Background/Purpose:

Recent experimental evidence using an animal model of rheumatoid arthritis (RA) has shown that platelet-derived microparticles exacerbate joint inflammation following engagement of the platelet-specific glycoprotein (GP) VI receptor by collagen (1). We have previously shown that GPVI engagement by collagen causes shedding of the soluble extracellular domain of GPVI (sGPVI) (2). Therefore we set out to evaluate 1) platelet aggregation in response to collagen and 2) plasma sGPVI levels in patients with RA.

Methods:

Patients with an established diagnosis of RA were recuited consecutively. Those with a history of cardiovascular disease or who were receiving anti-platelet therapy or thromboembolic prophylaxis were excluded. Disease activity was assessed using standard inflammatory biomarkers and the internationally validated DAS-28 score. Platelet aggregation in response to increasing doses of collagen was tested in RA(n=62) patients and healthy controls (n=80). We also measured sGPVI levels by ELISA in double-spun plasma from a subset of these RA patients (n=10) and controls (n=20).

Conclusion:

Patients with RA have decreased platelet response to GPVI stimulation by collagen compared to controls. Furthermore, levels of sGPVI are dramatically elevated in RA. This implies enhanced activity of the platelet GPVI pathway in RA, a phenomenon that could contribute to the underlying thrombotic risk in this patient population.